Aspiration pneumonia was the most frequent cause of death in older patients with <scp>SARS‐CoV</scp> ‐2 omicron‐related pneumonia in Japan

Abstract

Aspiration pneumonia is a major problem in Japan because there are many older persons who have conditions that predispose them to swallowing dysfunction and progression of super-aging.1, 2 Japanese older persons who receiving care because of comorbid illnesses often suffering from aspiration pneumonia due to respiratory tract infection.3 During the period when the SARS-CoV-2 ancestral Alpha variant and later Delta variant were dominant, bacterial coinfection in patients with COVID-19-related pneumonia was low.4, 5 In the Omicron period, however, the pattern of pneumonia changed from primarily viral pneumonia to bacterial coinfection, mainly aspiration pneumonia in older patients. In this study, we investigated the frequency of bacterial coinfection and aspiration and cause of death in older patients hospitalized for COVID-19-related pneumonia. The present study was conducted at five institutions between February 2020 and October 2023. COVID-19 was diagnosed using positive reverse transcription polymerase chain reaction (RT-PCR) results in accordance with the protocol recommended by the National Institute of Infectious Diseases, Japan. Identification of SARS-CoV-2 variants was performed by Sanger sequencing of the spike coding gene using an ABI 3500 analyzer (Applied Biosystems). We enrolled older patients (≥ 65 years old) consecutively diagnosed with pneumonia who were SARS-CoV-2 RT-PCR positive. When the RT-PCR for SARS-CoV-2 was positive, microbiological tests were performed as described previously.6 COVID-19 pneumonia with mixed bacteria was defined if one of the following conditions was present:7 (1) blood or pleural fluid cultures yielded the presence of a bacterial pathogen; (2) urinary antigen test results were positive for Legionella pneumophila or Streptococcus pneumoniae; (3) respiratory specimen culture results were positive for Mycoplasma pneumoniae, Chlamydia, or Legionella species; (4) a fourfold increase in the antibody titer for M. pneumoniae, Legionella species, Coxiella burnetii, or Chlamydia species (IgM or IgG) was determined using paired serum samples; or (5) an organism showing heavy (≥107 cfu/mL) or moderate (106 cfu/mL) growth of a predominant bacterium on a sputum culture in combination with Gram stain findings. Aspiration pneumonia was defined in accordance with the Japanese Study Group on Aspiration Pulmonary Disease definition as pneumonia in a patient with a predisposition to aspiration because of dysphagia or swallowing disorders.3 Swallowing function was assessed using the water swallowing test, repetitive saliva swallowing test, simple-swallowing provocation test, and video fluorography.2, 3 When swallowing function was not assessed using these examinations, the presence of overt symptoms of dysphagia or a medical history of aspiration was determined as a swallowing disorder in the patient. During the study period, 2179 older patients with COVID-19-related pneumonia (301 ancestral strain, 209 Alpha variant, 74 Delta variant, and 1595 Omicron variant) were recognized (Table 1). Among COVID-19-related pneumonia cases, primary viral pneumonia was the most frequently observed until the Delta variant (Figure 1). With the replacement of the Delta variant by the Omicron variant, the proportion of aspiration pneumonia increased significantly from 4% to 41% (p < 0.0001). Primary viral pneumonia was the most frequent cause of death among COVID-19-related pneumonia cases until the Delta variant (Table 1). During the Omicron period, the most frequent cause of death changed from primary viral pneumonia at 3.3% to aspiration pneumonia at 5.7%. The SARS-CoV-2 Omicron variant showed decreased infectivity in the lungs and was less pathogenic compared with the Delta variant and ancestral SARS-CoV-2 in a hamster model.8 In addition, vaccination against SARS-CoV-2 progressed and the mortality rate dropped markedly in Japan.9 However, the highest number of deaths was observed in older patients during the Omicron period. The present study demonstrated that the mortality rate decreased in the primary Omicron variant pneumonia group compared with the primary ancestral strain and the Alpha and Delta variant pneumonia group. On the other hand, aspiration pneumonia was significantly increased among COVID-19-related pneumonia cases in the Omicron period. In contrast to Delta and the former variant, the Omicron variant has lower viral replication competence in the lungs compared with the bronchi which is of particular interest.10 This difference was also confirmed by immunohistochemistry studies showing lower levels of virus-infected cells in human lung explant cultures ex vivo.10 Increased affinity for the bronchi with the Omicron variant may explain the reduced mortality rate, but increased aspiration pneumonia in the older patients. Advanced age and medical comorbidities have been associated with aspiration pneumonia in Japan, a super-aging society.2, 3 Thus, the Japanese Respiratory Society pneumonia guidelines emphasize the importance of pneumonia prevention rather than antibiotic therapy reflecting a super-aging society.3, 7 Physicians should recommend SARS-CoV-2 vaccination and non-pharmaceutical interventions for older persons even when the predominant strain is the Omicron variant. Naoyuki Miyashita and Yasushi Nakamori; Concept and Design. Naoyuki Miyashita and Tomoki Ito; Preparation of manuscript. All authors; Recruitment of subjects. Yasushi Nakamori, Makoto Ogata, Naoki Fukuda and Akihisa Yamura; Data collection. Fukuda and Akihisa Yamura; Analyzing Data. All authors; Creating the final version of the manuscript. We gratefully acknowledge members of the participating facilities for providing detailed clinical information on the cases of COVID-19 pneumonia. The authors declare that they have no competing interests. No funding was received. The data will not be shared because of participant confidentiality.

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